tbuckley/cabot-search huggingface dataset:
Anti–Citrullinated Protein Antibodies With Multiple Specificities Ameliorate Collagen Antibody–Induced Arthritis in a <scp>Time‐Dependent</scp> Manner
Authors: Alejandro M. Gomez, R. Camille Brewer, Jae‐Seung Moon, Suman Acharya, Sarah Kongpachith, Qian Wang, Shaghayegh Jahanbani, Heidi H. Wong, Tobias V. Lanz, Zelda Z. Love, Gundula Min‐Oo, Anita Niedziela‐Majka, William H. Robinson
Journal: Arthritis & Rheumatology (2023)

Objective Anti–citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and have long been regarded as pathogenic. Despite substantial in vitro evidence supporting this claim, reports investigating the proinflammatory effects of ACPAs in animal models of arthritis are rare and include mixed results. Here, we sequenced the plasmablast antibody repertoire of a patient with RA and functionally characterized the encoded ACPAs. Methods We expressed ACPAs from the antibody repertoire of a patient with RA and characterized their autoantigen specificities on antigen arrays and enzyme‐linked immunosorbent assays. Binding affinities were estimated by bio‐layer interferometry. Select ACPAs (n = 9) were tested in the collagen antibody–induced arthritis (CAIA) mouse model to evaluate their effects on joint inflammation. Results Recombinant ACPAs bound preferentially and with high affinity (nanomolar range) to citrullinated (cit) autoantigens (primarily histones and fibrinogen) and to auto‐cit peptidylarginine deiminase 4 (PAD4). ACPAs were grouped for in vivo testing based on their predominant cit‐antigen specificities. Unexpectedly, injections of recombinant ACPAs significantly reduced paw thickness and arthritis severity in CAIA mice as compared with isotype‐matched control antibodies ( P ≤ 0.001). Bone erosion, synovitis, and cartilage damage were also significantly reduced ( P ≤ 0.01). This amelioration of CAIA was observed for all the ACPAs tested and was independent of cit‐PAD4 and cit‐fibrinogen specificities. Furthermore, disease amelioration was more prominent when ACPAs were injected at earlier stages of CAIA than at later phases of the model. Conclusion Recombinant patient‐derived ACPAs ameliorated CAIA. Their antiinflammatory effects were more preventive than therapeutic. This study highlights a potential protective role for ACPAs in arthritis. image
Development of a Machine Learning–Based Prescriptive Tool to Address Racial Disparities in Access to Care After Penetrating Trauma
Authors: Anthony Gebran, Sumiran S. Thakur, Lydia R. Maurer, Hari Bandi, Robert Sinyard, Ander Dorken-Gallastegi, Mary Bokenkamp, Mohamad El Moheb, Leon Naar, Annita Vapsi, Dania Daye, George C. Velmahos, Dimitris Bertsimas, Haytham M. A. Kaafarani
Journal: JAMA Surgery (2023)

The use of artificial intelligence (AI) in clinical medicine risks perpetuating existing bias in care, such as disparities in access to postinjury rehabilitation services.
Fatty Acids Support the Fitness and Functionality of Tumor-Resident CD8+ T Cells by Maintaining SCML4 Expression
Authors: Maoxiao Feng, Xiaoyan Liu, Xiaodong Hao, Yidan Ren, Guoying Dong, Jie Tian, Yuli Wang, Lutao Du, Yunshan Wang, Chuanxin Wang
Journal: Cancer Research (2023)

CD8+ tissue-resident memory T (Trm) cells and tumor-infiltrating lymphocytes (TIL) regulate tumor immunity and immune surveillance. Characterization of Trm cells and TILs could help identify potential strategies to boost antitumor immunity. Here, we found that the transcription factor SCML4 was required for the progression and polyfunctionality of Trm cells and was associated with a better prognosis in patients with cancer. Moreover, SCML4 maintained multiple functions of TILs. Increased expression of SCML4 in CD8+ cells significantly reduced the growth of multiple types of tumors in mice, while deletion of SCML4 reduced antitumor immunity and promoted CD8+ T-cell exhaustion. Mechanistically, SCML4 recruited the HBO1-BRPF2-ING4 complex to reprogram the expression of T cell-specific genes, thereby enhancing the survival and effector functions of Trm cells and TILs. SCML4 expression was promoted by fatty acid metabolism through mTOR-IRF4-PRDM1 signaling, and fatty acid metabolism-induced epigenetic modifications that promoted tissue-resident and multifunctional gene expression in Trm cells and TILs. SCML4 increased the therapeutic effect of anti-PD-1 treatment by elevating the expression of effector molecules in TILs and inhibiting the apoptosis of TILs, which could be further enhanced by adding an inhibitor of H3K14ac deacetylation. These results provide a mechanistic perspective of functional regulation of tumor-localized Trm cells and TILs and identify an important activation target for tumor immunotherapy.SCML4 upregulation in CD8+ Trm cells and tumor-infiltrating lymphocytes induced by fatty acid metabolism enhances antitumor immune responses, providing an immunometabolic axis to target for cancer treatment. See related commentary by Chakraborty et al., p. 3321.
Air Pollution Might Contribute to Antibiotic Resistance
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Written Exposure Therapy Finds Solid Footing Alongside First-Line Psychotherapies for Posttraumatic Stress Disorder
Authors: Charles T. Taylor, Murray B. Stein
Journal: JAMA Psychiatry (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Carbohydrate quality, fecal microbiota and cardiometabolic health in older adults: a cohort study
Authors: Alessandro Atzeni, Stephanie K. Nishi, Nancy Babio, Clara Belzer, Prokopis Konstanti, Jesús Vioque, Dolores Corella, Olga Castañer, Josep Vidal, Isabel Moreno-Indias, Laura Torres-Collado, Eva M. Asensio, Montserrat Fitó, Ana Maria Gomez-Perez, Alejandro Arias, Miguel Ruiz-Canela, Frank B. Hu, Francisco J. Tinahones, Jordi Salas-Salvadó
Journal: Gut Microbes (2023)

The impact of carbohydrate quality, measured by the carbohydrate quality index (CQI), on gut microbiota and health has been scarcely investigated. The aim of this study was to cross-sectionally and longitudinally explore the relationships between CQI, fecal microbiota, and cardiometabolic risk factors in an elderly Mediterranean population at high cardiovascular risk. At baseline and 1-year, CQI was assessed from food frequency questionnaires data, cardiometabolic risk factors were measured, and fecal microbiota profiled from 16S sequencing. Multivariable-adjusted linear regression models were fitted to assess the associations between tertiles of baseline CQI, fecal microbiota, and cardiometabolic risk factors at baseline, and between tertiles of 1-year change in CQI, 1-year change in fecal microbiota and cardiometabolic risk factors. Cross-sectionally, higher CQI was positively associated with Shannon alpha diversity index, and abundance of genera Faecalibacterium and Christensenellaceae R7 group, and negatively associated with the abundance of Odoribacter, and uncultured Rhodospirillales genera. Some of these genera were associated with higher glycated hemoglobin and lower body mass index. In addition, we observed a positive association between CQI, and some pathways related with the metabolism of butyrate precursors and plants-origin molecules. Longitudinally, 1-year improvement in CQI was associated with a concurrent increase in the abundance of genera Butyrivibrio. Increased abundance of this genera was associated with 1-year improvement in insulin status. These observations suggest that a better quality of carbohydrate intake is associated with improved metabolic health, and this improvement could be modulated by greater alpha diversity and abundance of specific genera linked to beneficial metabolic outcomes.
Elevation of <scp>IL</scp>‐17 Cytokines Distinguishes Kawasaki Disease From Other Pediatric Inflammatory Disorders
Authors: Kailey E. Brodeur, Meng Liu, Daniel Ibanez, Mareike J. de Groot, Liang Chen, Yan Du, Eman Seyal, Raquel Laza‐Briviesca, Annette Baker, Joyce C. Chang, Margaret H. Chang, Megan Day‐Lewis, Fatma Dedeoglu, Audrey Dionne, Sarah D. de Ferranti, Kevin G. Friedman, Olha Halyabar, Mindy S. Lo, Esra Meidan, Robert P. Sundel, Lauren A. Henderson, Peter A. Nigrovic, Jane W. Newburger, Mary Beth Son, Pui Y. Lee
Journal: Arthritis & Rheumatology (2023)

Kawasaki disease (KD) is a systemic vasculitis of young children that can lead to development of coronary artery aneurysms. We aimed to identify diagnostic markers to distinguish KD from other pediatric inflammatory diseases.
Multi-omics analysis revealing the interplay between gut microbiome and the host following opioid use
Authors: Udhghatri Kolli, Richa Jalodia, Shamsudheen Moidunny, Praveen Kumar Singh, Yuguang Ban, Junyi Tao, Gonzalo Nathaniel Cantu, Eridania Valdes, Sundaram Ramakrishnan, Sabita Roy
Journal: Gut Microbes (2023)

Opioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover the role of opioid-induced dysbiosis in disrupting intestinal homeostasis we utilized whole genome sequencing, untargeted metabolomics, and mRNA sequencing to identify changes in microbiome, metabolome, and host transcriptome respectively. Morphine treatment resulted in significant expansion of Parasuterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and depletion of Lactobacillus johnsonii. These changes correlated with alterations in lipid metabolites and flavonoids. Significant alteration in microbial metabolism (metabolism of lipids, amino acids, vitamins and cofactors) and increased expression of virulence factors and biosynthesis of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) were observed in microbiome of morphine-treated animals. In concurrence with changes in microbiome and metabolome extensive changes in innate and adaptive immune response, lipid metabolism, and gut barrier dysfunction were observed in the host transcriptome. Microbiome depleted mice displayed lower levels of inflammation, immune response and tissue destruction compared to mice harboring a dysbiotic microbiome in response to morphine treatment, thus establishing dysbiotic microbiome as mediator of morphine gut pathophysiology. Integrative analysis of multi-omics data highlighted the associations between Parasutterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and altered levels of riboflavin, flavonoids, and lipid metabolites including phosphocholines, carnitines, bile acids, and ethanolamines with host gene expression changes involved in inflammation and barrier integrity of intestine. Omic analysis also highlighted the role of probiotic bacteria Lactobacillus johnsonii, metabolites flavonoids and riboflavin that were depleted with morphine as important factors for intestinal homeostasis. This study presents for the first time ever an interactive view of morphine-induced changes in microbial metabolism, strain level gut microbiome analysis and comprehensive view of changes in gut transcriptome. We also identified areas of potential therapeutic interventions to limit microbial dysbiosis and present a unique resource to the opioid research community.
Matrix Stiffness Triggers Lipid Metabolic Cross-talk between Tumor and Stromal Cells to Mediate Bevacizumab Resistance in Colorectal Cancer Liver Metastases
Authors: Yannan Zheng, Rui Zhou, Jianan Cai, Nanyan Yang, Zhaowei Wen, Zhihua Zhang, Huiying Sun, Genjie Huang, Yijin Guan, Na Huang, Min Shi, Yulin Liao, Jianping Bin, Wangjun Liao
Journal: Cancer Research (2023)

Bevacizumab is an anti-VEGF monoclonal antibody that plays an important role in the combination treatment of advanced colorectal cancer. However, resistance remains a major hurdle limiting bevacizumab efficacy, highlighting the importance of identifying a mechanism of antiangiogenic therapy resistance. Here, we investigated biophysical properties of the extracellular matrix (ECM) related to metabolic processes and acquired resistance to bevacizumab. Evaluation of paired pre- and posttreatment samples of liver metastases from 20 colorectal cancer patients treated with combination bevacizumab therapy, including 10 responders and 10 nonresponders, indicated that ECM deposition in liver metastases and a highly activated fatty acid oxidation (FAO) pathway were elevated in nonresponders after antiangiogenic therapy compared with responders. In mouse models of liver metastatic colorectal cancer (mCRC), anti-VEGF increased ECM deposition and FAO in colorectal cancer cells, and treatment with the FAO inhibitor etomoxir enhanced the efficacy of antiangiogenic therapy. Hepatic stellate cells (HSC) were essential for matrix stiffness-mediated FAO in colon cancer cells. Matrix stiffness activated lipolysis in HSCs via the focal adhesion kinase (FAK)/yes-associated protein (YAP) pathway, and free fatty acids secreted by HSCs were absorbed as metabolic substrates and activated FAO in colon cancer cells. Suppressing HSC lipolysis using FAK and YAP inhibition enhanced the efficacy of anti-VEGF therapy. Together, these results indicate that bevacizumab-induced ECM remodeling triggers lipid metabolic cross-talk between colon cancer cells and HSCs. This metabolic mechanism of bevacizumab resistance mediated by the physical tumor microenvironment represents a potential therapeutic target for reversing drug resistance.Extracellular matrix stiffening drives bevacizumab resistance by stimulating hepatic stellate cells to provide fuel for mCRC cells in the liver, indicating a potential metabolism-based therapeutic strategy for overcoming resistance.
Risk factors of extubation failure in neurocritical patients with the most impaired consciousness
Authors: Hugues de Courson, Nicolas Massart, Karim Asehnoune, Raphaël Cinotti, Paër-sélim Abback, Anaïs Codorniu, Giuseppe Citerio, Vittoria Ludovica Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Jessica Giuseppina Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Chiara Robba, Denise Battaglini, Patrick Biston, Mohamed Fathi Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter van Vliet, Benjamin Marcel Gerretsen, Iris Xochitl Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, Wytze J. Vermeijden, Alexander Daniel Cornet, Sergio Reyes Inurrigarro, Rafael Cirino Lara Domínguez, Maria Mercedes Bellini, Maria Milagros Gomez Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Roberto Carlos Miranda-Ackerman, Francisco José Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Hana Basheer Yahya, Ala Khaled, Mohamed Ghula, Cracchiolo Neville Andrea, Palma Maria Daniela, Cristian Deana, Luigi Vetrugno, Manuel J. Rivera Chavez, Rocio Mendoza Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu van der Jagt, Job van Steenkiste, Hazem Ahmed, Alexander Edward Coombs, Jessie Welbourne, Ana Alicia Velarde Pineda, Víctor Hugo Nubert Castillo, Mohammed A. Azab, Ahmed Y. Azzam, David Michael Paul van Meenen, Gilberto Adrian Gasca, Alfredo Arellano, Forttino Galicia-Espino-sa, José Carlos García-Ramos, Ghanshyam Yadav, Amarendra Kumar Jha, Vincent Robert-Edan, Pierre-Andre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal, Yashbir Deewan, Gilberto Adrian Gasca, Alfredo Arellano, Syed Tariq Reza, Md. Mozaffer Hossain, Christos Papadas, Vasiliki Chantziara, Chrysanthi Sklavou, Yannick Hourmant, Nicolas Grillot, Romain Pirracchio, Abdelraouf Akkari, Mohamed Abdelaty, Ahmed Hashim, Yoann Launey, Elodie Masseret, Sigismond Lasocki, Soizic Gergaud, Nicolas Mouclier, Sulekha Saxena, Avinash Agrawal, Shakti Bedanta Mishra, Samir Samal, Romain Pirracchio, Nicholas Fong, Jean Digitale, Robert Stevens, Julio Cesar Mijangos, Matthias Haënngi, Mohan Gurjar, Marcus Schultz, Daniel Agustin Godoy, Pablo Alvarez, Callum Kaye, Aikaterini Ioakeimidou, Yoshitoyo Ueno, Rafael Badenes, Abdurrahmaan Suei Elbuzidi, Michael Piagnerelli, Muhammed Elhadi, Ricardo Cerda, Norma Peredo
Journal: Intensive Care Medicine (2023)
Defining a Precise Diagnostic Strategy for Suspected Coronary Artery Disease—Lessons Learned From the PRECISE Trial
Authors: Krishna K. Patel, Leslee J. Shaw
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Deferred Testing in Stable Outpatients With Suspected Coronary Artery Disease
Authors: James E. Udelson, Michelle D. Kelsey, Michael G. Nanna, Christopher B. Fordyce, Eric Yow, Robert M. Clare, Daniel B. Mark, Manesh R. Patel, Campbell Rogers, Nick Curzen, Gianluca Pontone, Pál Maurovich-Horvat, Bernard De Bruyne, John P. Greenwood, Victor Marinescu, Jonathon Leipsic, Gregg W. Stone, Ori Ben-Yehuda, Colin Berry, Shea E. Hogan, Bjorn Redfors, Ziad A. Ali, Robert A. Byrne, Christopher M. Kramer, Robert W. Yeh, Beth Martinez, Sarah Mullen, Whitney Huey, Kevin J. Anstrom, Hussein R. Al-Khalidi, Karen Chiswell, Sreekanth Vemulapalli, Pamela S. Douglas, Michael Barry, Stephen Bloom, David Buck, Jane Cao, Jeffrey Carstens, Justin Carter, Benjamin Chow, George Chrysant, Jason Cole, Derek Connolly, Ryan Daly, Sorin Danciu, Melissa Daubert, Roderick Deano, Peter Fail, Timothy Fairbairn, Maros Ferencik, Thomas Hauser, Peter Haworth, Mohammad Hojjati, Angela Hoye, Mark Ibrahim, Fuad Jan, Clemens Kadalie, Dinesh Kalra, Ronald Karlsberg, Steven Kindsvater, John Kobayashi, David Landers, James Lee, Diana Litmanovich, Scott Matson, David McAllister, Gerald McCann, Mark Meier, Nicolai Mejevoi, Bela Merkely, Jamaluddin Moloo, Michael Morris, Darra Murphy, Nasar Nallamothu, Anna Narezkina, Katarina Nelson, Tuan Nguyen, Koen Nieman, Prabhjot Nijjar, Peter O'Kane, Amit Patel, Hena Patel, Thomas Phiambolis, Amit Pursnani, Mark Rabbat, Steven Raible, Frederic Resnic, Michael Salerno, Daniel Sauri, Uwe O.P.J. Schoepf, Moneal Shah, Vincent Sorrell, Michael Turner, Michael Walls, Jonathan Weir-McCall, Frederick Welt, Andrew Zurick
Journal: JAMA Cardiology (2023)

Guidelines recommend deferral of testing for symptomatic people with suspected coronary artery disease (CAD) and low pretest probability. To our knowledge, no randomized trial has prospectively evaluated such a strategy.